CN109503517A - 一种沃替西汀α晶型的制备方法 - Google Patents

一种沃替西汀α晶型的制备方法 Download PDF

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Publication number
CN109503517A
CN109503517A CN201710826791.7A CN201710826791A CN109503517A CN 109503517 A CN109503517 A CN 109503517A CN 201710826791 A CN201710826791 A CN 201710826791A CN 109503517 A CN109503517 A CN 109503517A
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Prior art keywords
vortioxetine
crystal form
alpha
preparation
hydrobromate
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赵林
赵国磊
赵云萍
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Wanquan Pharmaceutical (xiamen) Co Ltd Wante
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Wanquan Pharmaceutical (xiamen) Co Ltd Wante
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明属于药物化学领域，旨在提供一种沃替西汀氢溴酸盐的制备方法，将样品置于先以乙酸乙酯为溶剂成氢溴酸盐，得到的氢溴酸盐在有机溶剂中加热回流，冷却析晶，得到沃替西汀α晶型。本发明丰富了其晶型的研究，能够使医药研发工作者在沃替西汀晶型研究过程具有全面的了解和掌控。

Description

一种沃替西汀α晶型的制备方法
技术领域
本发明属于医药技术、晶型药物领域，具体涉及抗抑郁药物沃替西汀氢溴酸晶型的研究。
背景技术
沃替西汀 (vortioxetine)，化学名1-[2-（2,4-二甲基苯基硫基）苯基]哌嗪氢溴酸盐，适用于重度抑郁症的治疗，2013年9月美国食品药品监督管理局(FDA)批准其上市，商品名为Latuda，其分子式如下：
药物多晶型的研究是新药研发、工艺设计以及药物剂型设计过程中非常重要的组成部分。充分了解某一药物多晶型的现象及各种晶型的性质，对于药物研发工作者根据生物利用度及稳定性在设计原料药及制剂的制备工艺时具有极大的帮助。同时也保证了药物的质量，为患者的安全用药提供了有力的保障。
发明内容
本发明公开了一种抗抑郁药物沃替西汀(化学式如下)的α晶型及其制备方法：
，
将样品置于先以乙酸乙酯为溶剂成氢溴酸盐，得到的氢溴酸盐在有机溶剂中加热回流，冷却析晶，得到沃替西汀α晶型。其中，有机溶剂可选甲醇、甲苯、乙醇、丙酮、乙酸丁酯中的一种或多种混合。溶剂：原料药=5：1-25：1
本发明的有益效果在于公开了一种抗抑郁药物沃替西汀α晶型。沃替西汀作为一种具有多晶型的药物，本发明丰富了其晶型的研究，能够使医药研发工作者在沃替西汀晶型研究过程具有全面的了解和掌控。
具体实施实例
以下结合实例对本发明进行更详细的描述，但不作为对本发明的限制。
实施例1
向单口瓶(100 mL)中加入异丙醇(AR，65mL)和沃替西汀氢溴酸盐(5g)，加热使其回流，回流一小时，降温，冷却析晶；析晶2h后抽滤，滤饼干燥16h，即得到沃替西汀α晶型。
实施例2
向三口瓶（100 mL)中加入甲醇（AR，25mL）和沃替西汀（5g），加热到50℃，维持该温度1h，趁热抽滤，将滤液转移至单口瓶中，加入氢溴酸，搅拌2h后，抽滤，滤饼干燥16h，即得到沃替西汀α晶型。
实施例3
向单口瓶(100 mL)中加入甲苯(AR，125mL)和沃替西汀氢溴酸盐(5g)，加热使其回流，回流一小时，降温，冷却析晶；析晶2h后抽滤，滤饼干燥16h，即得到沃替西汀α晶型。

Claims (3)

1.一种沃替西汀α晶型的制备方法：先以乙酸乙酯为溶剂成氢溴酸盐，得到的氢溴酸盐在有机溶剂中加热回流，冷却析晶，得到沃替西汀α晶型。
2.根据权利要求1所述制备方法，有机溶剂为甲醇、甲苯、乙醇、丙酮、乙酸丁酯中的一种或多种。
3.根据权利要求1所述制备方法，溶剂：原料药=5：1-25：1。
CN201710826791.7A 2017-09-14 2017-09-14 一种沃替西汀α晶型的制备方法 Pending CN109503517A (zh)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110156720A (zh) * 2018-02-12 2019-08-23 成都弘达药业有限公司 一种氢溴酸沃替西汀的微晶及其制备方法
CN110790727A (zh) * 2019-09-30 2020-02-14 杭州和康药业有限公司 一种氢溴酸沃替西汀α型晶体的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101472906A (zh) * 2006-06-16 2009-07-01 H.隆德贝克有限公司 作为用于治疗认知损伤的、具有结合的对血清素再吸收、5－ht3和5－ht1a活性的化合物的1－[2－(2,4－二甲基苯基硫烷基)－苯基]哌嗪

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101472906A (zh) * 2006-06-16 2009-07-01 H.隆德贝克有限公司 作为用于治疗认知损伤的、具有结合的对血清素再吸收、5－ht3和5－ht1a活性的化合物的1－[2－(2,4－二甲基苯基硫烷基)－苯基]哌嗪

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110156720A (zh) * 2018-02-12 2019-08-23 成都弘达药业有限公司 一种氢溴酸沃替西汀的微晶及其制备方法
CN110790727A (zh) * 2019-09-30 2020-02-14 杭州和康药业有限公司 一种氢溴酸沃替西汀α型晶体的制备方法

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